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Smooth muscle cell-specific knockout of neuropilin-1 impairs postnatal lung development and pathological vascular smooth muscle cell accumulation

Mahmoud, M; Evans, I M; Mehta, V; Pellet-Many, C; Paliashvili, K; Zachary, I

Authors

M Mahmoud

I M Evans

V Mehta

C Pellet-Many

K Paliashvili

I Zachary



Abstract

Neuropilin 1 (NRP1) is important for neuronal and cardiovascular development due to its role in conveying class 3 semaphorin and vascular endothelial growth factor signaling, respectively. NRP1 is expressed in smooth muscle cells (SMCs) and mediates their migration and proliferation in cell culture and is implicated in pathological SMC remodeling in vivo. To address the importance of Nrp1 for SMC function during development, we generated conditional inducible Nrp1 SMC-specific knockout mice. Induction of early postnatal SMC-specific Nrp1 knockout led to pulmonary hemorrhage associated with defects in alveogenesis and revealed a specific requirement for Nrp1 in myofibroblast recruitment to the alveolar septae and PDGF-AA-induced migration in vitro. Furthermore, SMC-specific Nrp1 knockout inhibited PDGF-BB-stimulated SMC outgrowth ex vivo in aortic ring assays and reduced pathological arterial neointima formation in vivo. In contrast, we observed little significant effect of SMC-specific Nrp1 knockout on neonatal retinal vascularization. Our results point to a requirement of Nrp1 in vascular smooth muscle and myofibroblast function in vivo, which may have relevance for postnatal lung development and for pathologies characterized by excessive SMC and/or myofibroblast proliferation.

Citation

Mahmoud, M., Evans, I. M., Mehta, V., Pellet-Many, C., Paliashvili, K., & Zachary, I. (2019). Smooth muscle cell-specific knockout of neuropilin-1 impairs postnatal lung development and pathological vascular smooth muscle cell accumulation. https://doi.org/10.1152/ajpcell.00405.2018

Journal Article Type Article
Acceptance Date Jan 7, 2019
Publication Date Mar 8, 2019
Deposit Date Jun 13, 2019
Publicly Available Date Nov 20, 2020
Journal AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
Peer Reviewed Peer Reviewed
Volume 316
Issue 3
Pages C424-C433
DOI https://doi.org/10.1152/ajpcell.00405.2018
Public URL https://rvc-repository.worktribe.com/output/1383216

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